1. Field of the Invention
The present invention relates to a time-of-flight mass spectrometer.
2. Description of Related Art
It is important to accurately measure the masses of ions created by an atmospheric-pressure ionization (API) technique such as electrospray ionization (ESI) or atmospheric-pressure chemical ionization (APCI) in identifying proteins and metabolic substances. Mass spectrometry relying on a time-of-flight mass spectrometer (TOFMS) can realize both high measurement accuracy and high throughput and so this spectrometry is a promising candidate for the used technique in such applications. Where a TOFMS is interfaced to an atmospheric-pressure ion source that generates ions by such an ionization method, the difference in degree of vacuum between them is as high as about 10 orders of magnitude. Therefore, a differential pumping chamber is mounted as an interface. In the atmospheric-pressure ion source, ionization occurs continuously and, therefore, a continuous ion stream flows into the differential pumping chamber and enters into the TOFMS. In the TOFMS, the continuous ion stream is accelerated in a pulsed manner, and mass analysis is performed by utilizing differences in flight time between ions with different mass-to-charge ratios, the differences being created when they travel to a detector. The ion stream velocities have a smaller distribution width in the orthogonal direction than in the direction of travel. Consequently, to achieve higher resolution, it is now customary to adopt an orthogonal acceleration time-of-flight mass spectrometer (oa-TOFMS) in which ions are accelerated in a direction orthogonal to the ion stream.
If a quadrupole mass filter and a collision cell are mounted in the differential pumping chamber of a TOFMS, a quadrupole-quadrupole time-of-flight mass spectrometer (QqTOFMS) (i.e., a hybrid quadrupole time-of-flight mass spectrometer) is built. In this instrument, precursor ions selected by the quadrupole mass filter are fragmented in the collision cell. A mass spectrum of the resulting product ions is observed in the time-of-flight mass analyzer. The structure of the precursor ions can be estimated from the spectrum.
However, the oa-TOFMS and QqTOFMS have the problem that their efficiency of utilization of ions is low. That is, only a part of the ion stream continuously entering the orthogonal acceleration region of the TOF mass analyzer is accelerated and so ion streams not accelerated cannot be detected by the detector. This results in ion loss.
In Chernushevich et al. U.S. Pat. No. 6,507,019, in order to reduce ion loss in the QqTOFMS, a method of installing an ion trap ahead of the orthogonal acceleration region is proposed. In this instrument, the collision cell is also used as the ion trap. Ions once trapped in the collision cell are expelled as pulses. When the ions expelled in a pulsed manner reach the orthogonal acceleration region, they are accelerated in the orthogonal direction. If the efficiency at which ions are expelled in a pulsed manner out of the ion trap (collision cell) is high, the efficiency of utilization of ions in the orthogonal acceleration region should be high. In this method, however, mass dispersion takes place while ions expelled out of the ion trap (collision cell) are going to the orthogonal acceleration region. The ions are dispersed both temporally and spatially. Lighter ions reach the orthogonal acceleration region earlier and vice versa. Therefore, only ions having masses lying within a narrow range of mass-to-charge ratios are accelerated orthogonally. If the efficiency of discharge out of the ion trap is high, the ions having mass-to-charge ratios lying in this narrow range provide improved detection intensity. The problem is that the other ions cannot be detected.
In Dresch et al. U.S. Pat. No. 5,689,111, a method of increasing the efficiency of utilization of ions by connecting an ion trap to an oa-TOFMS is proposed but this method suffers from a problem similar to the problem with the method of the Chernushevich et al. patent.
In JP-A-2005-183022, a method is proposed which realizes higher sensitivity of a quadrupole-quadrupole time-of-flight mass spectrometer (QqTOFMS) including a first trap made of the collision cell and a second trap disposed between the first trap and the orthogonal acceleration region while maintaining a wide range of mass-to-charge ratios. In this instrument, ions are sequentially mass-selected in the first trap and discharged into the second trap, where they are once trapped and expelled in a pulsed manner. If the trap period in the second trap is made shorter than the expelling time from the first trap, ions expelled from the second trap by a single expelling operation are narrowed in mass range. Because ion pulses having a narrower mass range are less affected by mass dispersion, the ions can be admitted into the detector efficiently by the orthogonal acceleration region. In this method, however, mass selection is done in the first trap and, therefore, the orthogonal acceleration must be done plural times in order to measure ions of all mass-to-charge ratios. Hence, this instrument is lower in throughput than the normal quadrupole-quadrupole time-of-flight mass spectrometer (QqTOFMS) capable of orthogonally accelerating ions of all mass-to-charge ions at a time.
In JP-A-2003-346706, a method is proposed which realizes high sensitivity over a wide range of mass-to-charge ratios when a three-dimensional (3D) quadrupole ion trap and an orthogonal acceleration time-of-flight mass spectrometer (oa-TOFMS) are connected. In this instrument, heavier ions can be expelled from the ion trap earlier by creating a potential difference between the two end caps of the 3D quadrupole ion trap and successively increasing the amplitude of the RF voltage on the ring electrode. On the other hand, lighter ions travel at higher speeds in the region extending from the ion trap to the orthogonal acceleration region and, therefore, ions can be admitted into the orthogonal acceleration region simultaneously without recourse to mass-to-charge ratio. In this method, ions must be focused at one point inside the ion trap for each mass-to-charge ratio before the ions are expelled out of the ion trap. This is based on the premise that a pseudopotential given by Eq. (5) JP-A-2003-346706 is formed but it is formed only within a range to which adiabatic approximation can be applied. This range of application is restricted by the value of q-parameter given in Eq. (2) of this patent document. However, this restriction is not taken into consideration in this patent document and so the range of mass-to-charge ratios of ions is, in practice, narrower than represented by Eq. (16) of this patent document. Furthermore, even if the pseudopotential is faulted, ions can be converged at one point inside the ion trap for each mass-to-charge ratio only in the case of a 3D quadrupole ion trap having a small trap capacity. The convergence is impossible with a 2D ion trap having a larger trap capacity.